Development and progression of psoriasiform dermatitis and systemic lesions in the flaky skin (fsn) mouse mutant.
Flaky skin (fsn) mutant mice were originally described as a mouse model for psoriasis accompanied by hematological abnormalities. However, homozygous (fsn/fsn) mice develop a number of other pathological changes. Systematic evaluation of over 300 fsn/fsn and normal littermate control (+/+ or +/fsn) mice was carried out to characterize these changes. Psoriasiform skin lesions were first evident as focal epidermal hyperplasia and inflammation at 2 weeks of age. These lesions became confluent and diffuse by 3-4 weeks of age and were associated with marked dermal infiltration of lymphocytes and small numbers of neutrophils and macrophages. Mast cell numbers increased significantly in the dermis from 2 weeks of age onward. Diffuse dermal neovascularization accompanied these cutaneous changes. Systemic lesions included progressive and massive papillomatosis of the stratified squamous epithelium of the forestomach, hyperplasia and dysplasia of the glandular stomach, increased apoptosis of cecal enterocytes, renal glomerulopathy associated with immune complex and complement deposition, testicular degeneration, mixed inflammatory cell infiltrates and fibrosis around portal triads in the liver, splenomegaly due to massive erythropoiesis, and granulomatous lymphadenitis. This spontaneous mouse mutation provides a useful model for modulating neovascularization and keratinocyte hyperproliferation, especially since the cutaneous changes resemble some forms of psoriasis in humans.
Sundberg
J P
JP
Jackson Laboratory, Bar Harbor, Me. 04609-1500, USA. jps@jax.org
France
M
M
Boggess
D
D
Sundberg
B A
BA
Jenson
A B
AB
Beamer
W G
WG
Shultz
L D
LD
D000375:Aging; D000818:Animals; D002432:Cecum / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains / Q000235:genetics*; D011565:Psoriasis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000473:pathology / Q000503:physiopathology*; D013154:Spleen / Q000473:pathology; D013270:Stomach / Q000473:pathology; D013737:Testis / Q000473:pathology